How to manage hyponatremia in patients taking bupropion (Wellbutrin)

Management of Hyponatremia in Patients Taking Bupropion

Bupropion should be discontinued immediately in patients who develop hyponatremia, as it is a documented but uncommon cause of hyponatremia that can be reversed with medication discontinuation. 1, 2, 3

Pathophysiology and Risk Assessment

Bupropion-induced hyponatremia appears to be related to syndrome of inappropriate antidiuretic hormone secretion (SIADH), similar to other antidepressants. Several case reports have documented this association, though it is less commonly recognized than hyponatremia with SSRIs 1, 4.

Risk factors that increase susceptibility to bupropion-induced hyponatremia include:

• Older age (particularly >65 years)
• Female sex
• Low body weight
• Concomitant use of other medications that can cause hyponatremia
• Polypharmacy with other antidepressants 4

Diagnostic Approach

When hyponatremia is detected in a patient taking bupropion:

1. Check serum sodium level and assess severity:

   • Mild (130-134 mmol/L)
   • Moderate (125-129 mmol/L)
   • Severe (<125 mmol/L) 5

2. Determine volume status (hypervolemic, euvolemic, or hypovolemic)

   • Most cases of drug-induced hyponatremia are euvolemic SIADH

3. Evaluate for symptoms:

   • Mild: Nausea, headache, weakness
   • Severe: Confusion, seizures, altered mental status 5, 6

4. Rule out other causes of hyponatremia:

   • Other medications (especially if on multiple antidepressants)
   • Medical conditions (heart failure, cirrhosis, hypothyroidism)
   • Excessive fluid intake

Management Algorithm

For Severe Symptomatic Hyponatremia (<125 mmol/L with neurological symptoms):

1. Discontinue bupropion immediately 1, 2
2. Administer 3% hypertonic saline with target correction of 4-6 mEq/L in first 1-2 hours
3. Do not exceed correction of 10 mEq/L in 24 hours to prevent osmotic demyelination syndrome 5, 6
4. Monitor serum sodium every 4-6 hours during correction
5. Consider nephrology consultation

For Moderate Hyponatremia (125-129 mmol/L):

1. Discontinue bupropion 1, 2
2. Implement fluid restriction (<1L/day) 5
3. Monitor serum sodium daily until improving
4. Consider alternative antidepressant with lower risk of hyponatremia (e.g., mirtazapine) 1

For Mild Hyponatremia (130-134 mmol/L):

1. Consider discontinuing bupropion, especially in elderly patients
2. Implement mild fluid restriction
3. Monitor serum sodium levels twice weekly until normalized
4. If bupropion is essential for treatment, consider close monitoring while continuing therapy

Medication Substitution

If antidepressant therapy must be continued after bupropion discontinuation:

• Mirtazapine is preferred as it has a lower risk of causing hyponatremia and may help with insomnia and weight loss that can accompany depression 1
• Avoid other antidepressants known to cause hyponatremia (especially SSRIs, SNRIs) if possible
• If another antidepressant is necessary, initiate at low dose with frequent sodium monitoring

Prevention and Monitoring

For patients starting bupropion who have risk factors for hyponatremia:

1. Check baseline serum sodium before initiating therapy
2. Recheck sodium within 2 weeks of starting treatment 1
3. Monitor more frequently in elderly patients, those on diuretics, or with low BMI
4. Educate patients about symptoms of hyponatremia that warrant immediate medical attention

Special Considerations

• Polypharmacy increases risk: Bupropion-induced hyponatremia risk is higher when combined with other antidepressants 4
• Elderly patients are particularly vulnerable and may present with falls, confusion, or cognitive changes rather than classic hyponatremia symptoms 1, 6
• Chronic mild hyponatremia can lead to osteoporosis, gait disturbances, and increased fracture risk 6

By promptly recognizing and addressing bupropion-induced hyponatremia, clinicians can prevent serious complications and ensure appropriate management of patients' underlying psychiatric conditions.